Asymmetric remote hydroalkylation of unactivated olefins to aliphatic amines with minimally different substituents

Catalytic construction of enantiopure molecules with minimally differentiated substituents from abundant feedstocks remains a substantial challenge in asymmetric catalysis. Achieving precise enantiodiscrimination between alkyl groups is even more difficult owing to their very similar steric and electronic properties. In this study, we introduce a simple Earth-abundant nickel catalyst for the asymmetric remote C(sp3)–H alkylation of abundant and readily available unactivated alkenes to afford value-added, highly enantioenriched α-chiral alkyl amines of interest in pharmaceutical research and other areas. The reaction design includes the simple and common phthalimide motif as a driving force to enable challenging remote hydrofunctionalization of unactivated olefins in a highly regio- and enantioselective (up to 98% ee) manner while serving as an ammonia surrogate. This mild and modular platform demonstrates a wide substrate scope, good functional group compatibility, and the notable ability that discriminates between pairs of minimally differentiated alkyl groups bound to the amine, such as ethyl and n-propyl, and even subtler distinctions, such as n-butyl and halogenated butyl. Mechanistic studies indicate that exceptional stereoselectivity arises from cooperative noncovalent interactions between the ligand and the substrate.